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Background: Pregnancy poses specific challenges in the diagnosis of Plasmodium falciparum infection due to parasite sequestration in the placenta. The diagnosis of Plasmodium falciparum infection in pregnant mothers therefore requires highly sensitive methods in order to detect the presence of parasites. These include those that detect the presence of antigens and those that detect and quantify the presence of the malaria parasites. Objective: The study assessed the performance of mRDT diagnostic test ((PfHRP2 -RDT) in the detection of malaria infection in blood samples from nulliparous pregnant women within the first trimester of pregnancy in Western Kenya. Methods: This was a prospective study on blood specimens collected from pregnant women in a malaria-endemic region in Kenya. m-polymerase chain reaction (mPCR) and mRDT tests were performed. The diagnostic accuracy of m-RDT was compared with mPCR as the gold standard for the purpose of this study. Setting: Twelve primary health facilities in Busia, Bungoma and Kakamega Counties in Kenya Results: Out of 264 mPCR positive samples, 130 were mRDT positive (true positives) while 134 were mRDT negative (false negative). And out of 441 mPCR negative samples, 41 were positive on mRDT (false positive). Thus, in comparison with mPCR, the sensitivity and specificity of mRDT to detect malaria infection in nulliparous pregnant mothers in first trimester was 49.2% and 88.9% respectively Conclusions: The sensitivity of mRDT to detect Plasmodium falciparum infections in nulliparous pregnant mothers in the first trimester was not satisfactory compared to mPCR tests. [ABSTRACT FROM AUTHOR]

Background Assessing the infectious reservoir is critical in malaria control and elimination strategies. We conducted a longitudinal epidemiological study in a high-malaria-burden region in Kenya to characterize transmission in an asymptomatic population. Methods 488 study participants encompassing all ages in 120 households within 30 clusters were followed for 1 year with monthly sampling. Malaria was diagnosed by microscopy and molecular methods. Transmission potential in gametocytemic participants was assessed using direct skin and/or membrane mosquito feeding assays, then treated with artemether-lumefantrine. Study variables were assessed using mixed-effects generalized linear models. Results Asexual and sexual parasite data were collected from 3792 participant visits, with 903 linked with feeding assays. Univariate analysis revealed that the 6–11-year-old age group was at higher risk of harboring asexual and sexual infections than those <6 years old (odds ratio [OR] 1.68, P <.001; and OR 1.81, P <.001), respectively. Participants with submicroscopic parasitemia were at a lower risk of gametocytemia compared with microscopic parasitemia (OR 0.04, P <.001), but they transmitted at a significantly higher rate (OR 2.00, P =.002). A large proportion of the study population who were infected at least once remained infected (despite treatment) with asexual (71.7%, 291/406) or sexual (37.4%, 152/406) parasites. 88.6% (365/412) of feeding assays conducted in individuals who failed treatment the previous month resulted in transmissions. Conclusions Individuals with asymptomatic infection sustain the transmission cycle, with the 6–11-year age group serving as an important reservoir. The high rates of artemether-lumefantrine treatment failures suggest surveillance programs using molecular methods need to be expanded for accurate monitoring and evaluation of treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Low adoption of effective health technologies increases illness morbidity and mortality worldwide. In the case of malaria, effective tools such as malaria rapid diagnostic tests (RDTs) and artemisinin-combination therapies (ACTs) are both under-used and used inappropriately. Individuals' confidence in RDTs and ACTs likely affects the uptake of these tools.Methods: In a cohort of 36 households (280 individuals) in Western Kenya observed for 30 months starting in June 2017, we examined if experience with RDTs and ACTs changes people's beliefs about these technologies and how those beliefs affect treatment behavior. Household members requested a free RDT from the study team any time they suspected a malaria illness, and positive RDT results were treated with a free ACT. We conducted annual, monthly, and sick visit surveys to elicit beliefs about the accuracy of malaria RDT results and the effectiveness of ACTs. Beliefs were elicited on a 5-point Likert scale from "very unlikely" to "very likely."Results: Over the study period, the percentage of survey respondents that said a hypothetical negative RDT result was "very likely" to be correct increased from approximately 55% to 75%. Controlling for initial beliefs, people who had been tested at least once with an RDT in the past year had 3.6 times higher odds (95% CI [1 1.718 7.679], P = 0.001) of saying a negative RDT was "very likely" to be correct. Confidence in testing was associated with treatment behavior: those who believed a negative RDT was "very likely" to be correct had 1.78 times higher odds (95% CI [1.079 2.934], P = 0.024) of adhering to a negative RDT result (by not taking ACTs) than those who were less certain about the accuracy of negative RDTs. Adherence to a negative test also affected subsequent beliefs: controlling for prior beliefs, those who had adhered to their previous test result had approximately twice the odds (OR = 2.19, 95% CI [1.661 2.904], P < 0.001) of saying that a hypothetical negative RDT was "very likely" to be correct compared to those who had not adhered.Conclusions: Our results suggest that greater experience with RDTs can not only increase people's confidence in their accuracy but also improve adherence to the test result. [ABSTRACT FROM AUTHOR]

Spread of the Anopheles stephensi mosquito, an invasive malaria vector, threatens to put an additional 126 million persons per year in Africa at risk for malaria. To accelerate the early detection and rapid response to this mosquito species, confirming its presence and geographic extent is critical. However, existing molecular species assays require specialized laboratory equipment, interpretation, and sequencing confirmation. We developed and optimized a colorimetric rapid loop-mediated isothermal amplification assay for molecular An. stephensi species identification. The assay requires only a heat source and reagents and can be used with or without DNA extraction, resulting in positive color change in 30-35 minutes. We validated the assay against existing PCR techniques and found 100% specificity and analytical sensitivity down to 0.0003 ng of genomic DNA. The assay can successfully amplify single mosquito legs. Initial testing on samples from Marsabit, Kenya, illustrate its potential as an early vector detection and malaria mitigation tool.

Background: Screen-and-treat strategies with sensitive diagnostic tests may reduce malaria-associated adverse pregnancy outcomes. We conducted a diagnostic accuracy study to evaluate new point-of-care tests to screen pregnant women for malaria at their first antenatal visit in western Kenya.Methods: Consecutively women were tested for Plasmodium infection by expert microscopy, conventional rapid diagnostic test (cRDT), ultra sensitive RDT (usRDT), and loop-mediated isothermal amplification (LAMP). Photoinduced electron-transfer polymerase chain reaction (PET-PCR) served as the reference standard. Diagnostic performance was calculated and modelled at low parasite densities.Results: Between May and September 2018, 172 of 482 screened participants (35.7%) were PET-PCR positive. Relative to PET-PCR, expert microscopy was least sensitive (40.1%; 95% confidence interval [CI], 32.7%-47.9%), followed by cRDT (49.4%; 95% CI, 41.7%-57.1), usRDT (54.7%; 95% CI, 46.9%-62.2%), and LAMP (68.6%; 95% CI, 61.1%-75.5%). Test sensitivities were comparable in febrile women (n = 90). Among afebrile women (n = 392), the geometric-mean parasite density was 29 parasites/µL and LAMP (sensitivity = 61.9%) and usRDT (43.2%) detected 1.74 (95% CI, 1.31-2.30) and 1.21 (95% CI, 88-2.21) more infections than cRDT (35.6%). Per our model, tests performed similarly at densities >200 parasites/µL. At 50 parasites/µL, the sensitivities were 45%, 56%, 62%, and 74% with expert microscopy, cRDT, usRDT, and LAMP, respectively.Conclusions: This first-generation usRDT provided moderate improvement in detecting low-density infections in afebrile pregnant women compared to cRDTs. [ABSTRACT FROM AUTHOR]

Background: Understanding diagnostic capacities is essential to addressing healthcare provision and inequity, particularly in low-income and middle-income countries. This study used routine data to assess trends in rapid diagnostic test (RDT) reporting, supplies and unmet needs across national and 47 subnational (county) levels in Kenya., Methods: We extracted facility-level RDT data for 19 tests (2018-2020) from the Kenya District Health Information System, linked to 13 373 geocoded facilities. Data quality was assessed for reporting completeness (ratio of reports received against those expected), reporting patterns and outliers. Supply assessment covered 12 RDTs reported by at least 50% of the reporting facilities (n=5251), with missing values imputed considering reporting trends. Supply was computed by aggregating the number of tests reported per facility. Due to data limitations, demand was indirectly estimated using healthcare-seeking rates (HIV, malaria) and using population data for venereal disease research laboratory test (VDRL), with unmet need computed as the difference between supply and demand., Results: Reporting completeness was under 40% across all counties, with RDT-specific reporting ranging from 9.6% to 89.6%. Malaria RDTs showed the highest annual test volumes (6.3-8.0 million) while rheumatoid factor was the lowest (0.5-0.7 million). Demand for RDTs varied from 2.5 to 11.5 million tests, with unmet needs between 1.2 and 3.5 million. Notably, malaria testing and unmet needs were highest in Turkana County, as well as the western and coastal regions. HIV testing was concentrated in the western and central regions, with decreasing unmet needs from 2018 to 2020. VDRL testing showed high volumes and unmet needs in Nairobi and select counties, with minimal yearly variation., Conclusion: RDTs are crucial in enhancing diagnostic accessibility, yet their utilisation varies significantly by region. These findings underscore the need for targeted interventions to close testing gaps and improve data reporting completeness. Addressing these disparities is vital for equitably enhancing diagnostic services nationwide., Competing Interests: Competing interests: EO serves on the AstraZeneca Vaccine & Immune Therapies Effectiveness Evidence Scientific Advisory Committee (VEE-SAC)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Acute febrile illness (AFI) is a common reason for healthcare seeking and hospitalization in Sub-Saharan Africa and is often presumed to be malaria. However, a broad range of pathogens cause fever, and more comprehensive data on AFI etiology can improve clinical management, prevent unnecessary prescriptions, and guide public health interventions. We conducted surveillance for AFI (temperature ≥38.0°C <14 days duration) among hospitalized patients of all ages at four sites in Kenya (Nairobi, Mombasa, Kakamega, and Kakuma). For cases of undifferentiated fever (UF), defined as AFI without diarrhea (≥3 loose stools in 24 hours) or lower respiratory tract symptoms (cough/difficulty breathing plus oxygen saturation <90% or [in children <5 years] chest indrawing), we tested venous blood with real-time PCR-based TaqMan array cards (TAC) for 17 viral, 8 bacterial, and 3 protozoal fever-causing pathogens. From June 2017 to March 2019, we enrolled 3,232 AFI cases; 2,529 (78.2%) were aged <5 years. Among 3,021 with outcome data, 131 (4.3%) cases died while in hospital, including 106/2,369 (4.5%) among those <5 years. Among 1,735 (53.7%) UF cases, blood was collected from 1,340 (77.2%) of which 1,314 (98.1%) were tested by TAC; 715 (54.4%) had no pathogens detected, including 147/196 (75.0%) of those aged <12 months. The most common pathogen detected was Plasmodium, as a single pathogen in 471 (35.8%) cases and in combination with other pathogens in 38 (2.9%). HIV was detected in 51 (3.8%) UF cases tested by TAC and was most common in adults (25/236 [10.6%] ages 18-49, 4/40 [10.0%] ages ≥50 years). Chikungunya virus was found in 30 (2.3%) UF cases, detected only in the Mombasa site. Malaria prevention and control efforts are critical for reducing the burden of AFI, and improved diagnostic testing is needed to provide better insight into non-malarial causes of fever. The high case fatality of AFI underscores the need to optimize diagnosis and appropriate management of AFI to the local epidemiology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Human infection studies (HIS) that involve deliberately infecting healthy volunteers with a pathogen raise important ethical issues, including the need to ensure that benefits and burdens are understood and appropriately accounted for. Building on earlier work, we embedded social science research within an ongoing malaria human infection study in coastal Kenya to understand the study benefits and burdens experienced by study stakeholders in this low-resource setting and assess the wider implications for future research planning and policy.Methods: Data were collected using qualitative research methods, including in-depth interviews (44), focus group discussions (10) and non-participation observation. Study participants were purposively selected (key informant or maximal diversity sampling), including volunteers in the human infection study, study staff, community representatives and local administrative authorities. Data were collected during and up to 18 months following study residency, from sites in Coastal and Western Kenya. Voice recordings of interviews and discussions were transcribed, translated, and analysed using framework analysis, combining data- and theory-driven perspectives.Findings: Physical, psychological, economic and social forms of benefits and burdens were experienced across study stages. Important benefits for volunteers included the study compensation, access to health checks, good residential living conditions, new learning opportunities, developing friendships and satisfaction at contributing towards a new malaria vaccine. Burdens primarily affected study volunteers, including experiences of discomfort and ill health; fear and anxiety around aspects of the trial process, particularly deliberate infection and the implications of prolonged residency; anxieties about early residency exit; and interpersonal conflict. These issues had important implications for volunteers' families, study staff and the research institution's reputation more widely.Conclusion: Developing ethically and scientifically strong HIS relies on grounded accounts of volunteers, study staff and the wider community, understood in the socioeconomic, political and cultural context where studies are implemented. Recognition of the diverse, and sometimes perverse, nature of potential benefits and burdens in a given context, and who this might implicate, is critical to this process. Prior and ongoing stakeholder engagement is core to developing these insights. [ABSTRACT FROM AUTHOR]

Malaria rapid diagnostic tests (mRDTs) are an essential diagnostic tool in low-resource settings; however, administration and interpretation errors reduce their effectiveness. HealthPulse, a smartphone mRDT reader application, was developed by Audere to aid health workers in mRDT administration and interpretation, with an aim to improve the mRDT testing process and facilitate timely decision making through access to digitized results. Audere partnered with PSI and PS Kenya to conduct a pilot study in Busia County, Kenya between March and September 2021 to assess the feasibility and acceptability of HealthPulse to support malaria parasitological diagnosis by community health volunteers (CHVs) and private clinic health workers (private clinic HWs). Metadata was interpreted to assess adherence to correct use protocols and health worker perceptions of the app. Changes to mRDT implementation knowledge were measured through baseline and endline surveys. The baseline survey identified clear mRDT implementation gaps, such as few health workers correctly knowing the number of diluent drops and minimum and maximum wait times for mRDT interpretation, although health worker knowledge improved after using the app. Endline survey results showed that 99.6% of health workers found the app useful and 90.1% found the app easy to use. Process control data showed that most mRDTs (89.2%) were photographed within the recommended 30-minute time frame and that 91.4% of uploaded photos passed the app filter quality check on the first submission. During 154 encounters (3.5% of all encounters) a health worker dispensed an artemisinin-based combination therapy (ACT) to their patient even with a negative mRDT readout. Overall, study results indicated that HealthPulse holds potential as a mobile tool for use in low-resource settings, with future supportive supervision, diagnostic, and surveillance benefits. Follow-up studies will aim to more deeply understand the utility and acceptance of the HealthPulse app., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: SC, SS, and SF work for Audere. CL, MS, BK, TW, CO, and SP received funding from Audere. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2024 Skjefte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In the Lake Victoria basin of western Kenya, malaria remains highly endemic despite high coverage of interventions such as mass distribution of long-lasting insecticidal nets (LLIN), indoor residual spraying (IRS) programs, and improvement of availability and accessibility of rapid diagnostic tests (RDT) and artemisinin-based combination therapy (ACT) at community healthcare facilities. We hypothesize that one major cause of the residual transmission is the lack of motivation among residents for malaria prevention and early treatment., Methods: This study will aim to develop a demand-side policy tool to encourage local residents' active malaria prevention and early treatment-seeking behaviors. We examine the causal impact of a financial incentive intervention complemented with malaria education to residents in malaria-prone areas. A cluster-randomized controlled trial is designed to assess the effect of the financial incentive intervention on reducing malaria prevalence in residents of Suba South in Homa Bay County, Kenya. The intervention includes two components. The first component is the introduction of a financial incentive scheme tied to negative RDT results for malaria infection among the target population. This study is an attempt to promote behavioral changes in the residents by providing them with monetary incentives. The project has two different forms of incentive schemes. One is a conditional cash transfer (CCT) that offers a small reward (200 Ksh) for non-infected subjects during the follow-up survey, and the other is a lottery incentive scheme (LIS) that gives a lottery with a 10% chance of winning a large reward (2000 Ksh) instead of the small reward. The second component is a knowledge enhancement with animated tablet-based malaria educational material (EDU) developed by the research team. It complements the incentive scheme by providing the appropriate knowledge to the residents for malaria elimination. We evaluate the intervention's impact on the residents' malaria prevalence using a cluster-randomized control trial., Discussion: A policy tool to encourage active malaria prevention and early treatment to residents in Suba South, examined in this trial, may benefit other malaria-endemic counties and be incorporated as part of Kenya's national malaria elimination strategy., Trial Registration: UMIN000047728. Registered on 29th July 2022., (© 2024. The Author(s).)

Human malaria, caused by five Plasmodium species ( P. falciparum, P. vivax, P. malariae, P. ovale , and P. knowlesi ), remains a significant global health burden. While most interventions target P. falciparum , the species associated with high mortality rates and severe clinical symptoms, non-falciparum species exhibit different transmission dynamics, remain hugely neglected, and pose a significant challenge to malaria elimination efforts. Recent studies have reported the presence of antigens associated with cross-protective immunity, which can potentially disrupt the transmission of various Plasmodium species. With the sequencing of the Plasmodium genome and the development of immunoinformatic tools, in this study, we sought to exploit the evolutionary history of Plasmodium species to identify conserved cross-species B-cell linear epitopes in merozoite proteins. We retrieved Plasmodium proteomes associated with human malaria and applied a subtractive proteomics approach focusing on merozoite stage proteins. Bepipred 2.0 and Epidope were used to predict B-cell linear epitopes using P. falciparum as the reference species. The predictions were further compared against human and non-falciparum databases and their antigenicity, toxicity, and allergenicity assessed. Subsequently, epitope conservation was carried out using locally sequenced P. falciparum isolates from a malaria-endemic region in western Kenya (n=27) and Kenyan isolates from MalariaGEN version 6 (n=131). Finally, physiochemical characteristics and tertiary structure of the B-cell linear epitopes were determined. The analysis revealed eight epitopes that showed high similarity (70-100%) between falciparum and non-falciparum species. These epitopes were highly conserved when assessed across local isolates and those from the MalariaGEN database and showed desirable physiochemical properties. Our results show the presence of conserved cross-species B-cell linear epitopes that could aid in targeting multiple Plasmodium species. Nevertheless, validating their efficacy in-vitro and in-vivo experimentally is essential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest., (Copyright © 2024 Musundi, Gitaka and Kanoi.)

Pregnant women constitute a promising sentinel group for continuous monitoring of malaria transmission. To identify antibody signatures of recent Plasmodium falciparum exposure during pregnancy, we dissected IgG responses against VAR2CSA, the parasite antigen that mediates placental sequestration. We used a multiplex peptide-based suspension array in 2,354 samples from pregnant women from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. Two VAR2CSA peptides of limited polymorphism were immunogenic and targeted by IgG responses readily boosted during infection and with estimated half-lives of <2 years. Seroprevalence against these peptides reflected declines and rebounds of transmission in southern Mozambique during 2004-2012, reduced exposure associated with use of preventive measures during pregnancy, and local clusters of transmission that were missed by detection of P. falciparum infections. These data suggest that VAR2CSA serology can provide a useful adjunct for the fine-scale estimation of the malaria burden among pregnant women over time and space. [ABSTRACT FROM AUTHOR]

Abstract Rapid diagnostic tests (RDT) are valuable tools that support prudent and timely use of antimalarial drugs, particularly if reliable microscopy is not available. However, the performance and reliability of these tests vary between and within geographical regions. The present study evaluated the performance of routine malaria RDT in Kenyan febrile patients in Busia County, Kenya. A cross sectional study design was employed to recruit febrile patients attending health facilities between August and November 2016. A total of 192 febrile patients who were slide positive and negative were evaluated for their infection status by nested PCR and RDTs (PfHRP2/pLDH). In addition, P. falciparum diversity of the histidine-rich proteins 2 and 3, that influences the RDT test results were determined. All individuals were P. falciparum positive. Among the investigated 192 febrile patients, 76 (40%) were positive by microscopy, 101 (53%) by RDTs and 80 (42%) were PCR positive. The performance of the CareStart™ HRP2/pLDH (pf) RDTs was better than microscopy (Sensitivity 94%; Specificity 75%) and Nucleic acid testing (sensitivity 95%, specificity 77%) with high negative predictive values, indicating the suitability of the RDT in routine practice. Specific pfhrp2/pfhrp3 deletions shown to associate with RDT false negativity was not observed. However, high genetic diversity among pfhrp2 gene was observed. Eleven new PfHRP2 and nine PfHRP3 repeats were observed. False positivity by microscopy and under reporting of infections may thus be a barrier in malaria control and elimination programs. The HRP2/pLDH(Pf) based RDT yet demonstrate to be an effective tool for malaria surveillance program. Highlights • PfHRP2 and PfHRP3 rich amino acid diversity among Kenyan Plasmodium falciparum isolates. • Comparative evaluation of PfHRP2/pLDH malaria RDT with microscopy and nested PCR methodologies. • No PfHRP2 deletions observed in Kenyan isolates known to associate with RDT Sensitivity. • PfHRP2/pLDH RDT still an effective tool for malaria surveillance program in Kenya. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major cause of morbidity and mortality. Treatment of malaria in a timely manner could avert deaths. Treatment ultimately relies on the rapid and accurate diagnosis. Fluorescence in situ hybridization (FISH), a cytogenetic technique based on detection of specific nucleic acid, has the potential to address the limitations of the current diagnostic approaches. This study investigates further the performance of FISH for the diagnosis of malaria in a rural setting in Western Kenya.Methods: Blood samples from 302 patients presenting with fever (temperature ≥ 37.5 °C) were examined for malaria using the Giemsa microscopy (GM), rapid diagnostic test (RDT), polymerase chain reaction (PCR) and FISH.Results: The sensitivity and specificity of FISH was 85.6% and 96.2% respectively, while the corresponding values for GM were 82.2% and 100% respectively. RDT and PCR had sensitivities of 91.1% and 98.9%, respectively with their specificities being 89.6 and 100%, respectively. The positive predictive values for RDT, GM, FISH and PCR were 78.8%, 100%, 90.6% and 100%, respectively. The negative predictive values for RDT, GM, FISH and PCR were 96.0%, 93.0%, 94.0% and 99.5%, respectively. Their respective diagnostic accuracies were 90.1%, 94.7% 93.0% and 99.7%.Conclusion: The present study demonstrates that the specificity and reproducibility of FISH assays are high, thus adding to the growing evidence on the potential of the technique as an effective tool for the detection of malaria parasites in remote settings. [ABSTRACT FROM AUTHOR]

Background: Since 2004, Kenya's national malaria treatment guidelines have stipulated artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria, and since 2014, confirmatory diagnosis of malaria in all cases before treatment has been recommended. A number of strategies to support national guidelines have been implemented in the public and private sectors in recent years. A nationally-representative malaria outlet survey, implemented across four epidemiological zones, was conducted between June and August 2016 to provide practical evidence to inform strategies and policies in Kenya towards achieving national malaria control goals. Results: A total of 17,852 outlets were screened and 2271 outlets were eligible and interviewed. 78.3% of all screened public health facilities stocked both malaria diagnostic testing and quality-assured ACT (QAACT). Sulfadoxine- pyrimethamine (SP) for intermittent preventive treatment in pregnancy was available in 70% of public health facilities in endemic areas where it is recommended for treatment. SP was rarely found in the public sector outside of the endemic areas (< 0.5%). The anti-malaria stocking private sector had lower levels of QAACT (46.7%) and malaria blood testing (20.8%) availability but accounted for majority of anti-malarial distribution (70.6% of the national market share). More than 40% of anti-malarials were distributed by unregistered pharmacies (37.3%) and general retailers (7.1%). QAACT accounted for 58.2% of the total anti-malarial market share, while market share for non-QAACT was 15.8% and for SP, 24.8%. In endemic areas, 74.9% of anti-malarials distributed were QAACT. Elsewhere, QAACT market share was 49.4% in the endemic-prone areas, 33.2% in seasonal-transmission areas and 37.9% in low-risk areas. Conclusion: Although public sector availability of QAACT and malaria diagnosis is relatively high, there is a gap in availability of both testing and treatment that must be addressed. The private sector in Kenya, where the majority of anti-malarials are distributed, is also critical for achieving universal coverage with appropriate malaria case management. There is need for a renewed commitment and effective strategies to ensure access to affordable QAACT and confirmatory testing in the private sector, and should consider how to address malaria case management among informal providers responsible for a substantial proportion of the anti-malarial market share. [ABSTRACT FROM AUTHOR]

Background: Malaria control strategies need to respond to geographical hotspots of transmission. Detection of hotspots depends on the sensitivity of the diagnostic tool used.Methods: We conducted cross-sectional surveys in 3 sites within Kilifi County, Kenya, that had variable transmission intensities. Rapid diagnostic test (RDT), microscopy, and polymerase chain reaction (PCR) were used to detect asymptomatic parasitemia, and hotspots were detected using the spatial scan statistic.Results: Eight thousand five hundred eighty-one study participants were surveyed in 3 sites. There were statistically significant malaria hotspots by RDT, microscopy, and PCR for all sites except by microscopy in 1 low transmission site. Pooled data analysis of hotspots by PCR overlapped with hotspots by microscopy at a moderate setting but not at 2 lower transmission settings. However, variations in degree of overlap were noted when data were analyzed by year. Hotspots by RDT were predictive of PCR/microscopy at the moderate setting, but not at the 2 low transmission settings. We observed long-term stability of hotspots by PCR and microscopy but not RDT.Conclusion: Malaria control programs may consider PCR testing to guide asymptomatic malaria hotspot detection once the prevalence of infection falls. [ABSTRACT FROM AUTHOR]

Despite good progress towards elimination, malaria continues to contribute substantially to the sub-Saharan African disease burden. Sustaining previous gains requires continued readiness to deliver malaria services in response to actual disease burden, which in turn contributes to health systems strengthening. This study investigates a health system innovation. We examined whether malaria prevalence, or endemicity, is a driver of health facility readiness to deliver malaria services. To estimate this association, we geo-linked cross-sectional facility survey data to endemicity data for Kenya, Namibia and Senegal. We tested the validity and reliability of the primary study outcome, the malaria service readiness index and mapped service readiness components in a geographic information system. We conducted a weighted multivariable linear regression analysis of the relationship between endemicity and malaria service readiness, stratified for urban or rural facility location. As endemicity increased in rural areas, there was a concurrent, modest increase in service readiness at the facility level [β: 0.028; (95% CI 0.008, 0.047)], whereas no relationship existed in urban settings. Private-for-profit facilities were generally less prepared than public [β: -0.102; (95% CI - 0.154, -0.050)]. Most facilities had the necessary supplies to diagnose malaria, yet availability of malaria guidelines and adequately trained staff as well as medicines and commodities varied. Findings require cautious interpretation outside the study sample, which was a more limited subset of the original surveys' sampling schemes. Our approach and findings may be used by national malaria programs to identify low performing facilities in malarious areas for targeted service delivery interventions. This study demonstrates use of existing data sources to evaluate health system performance and to identify within- and cross-country variations for targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya. Methods: A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes. Results: The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children. Conclusion: Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels. [ABSTRACT FROM AUTHOR]

Background: Although use of malaria diagnostic tests has increased in recent years, health workers often prescribe anti-malarial drugs to individuals who test negative for malaria. This study investigates how health worker adherence to malaria case management guidelines influences individuals' beliefs about whether their illness was malaria, and their confidence in the effectiveness of artemisinin-based combination therapy (ACT). Methods: A survey was conducted with 2065 households in Western Kenya about a household member's treatment actions for a recent febrile illness. The survey also elicited the individual's (or their caregiver's) beliefs about the illness and about malaria testing and treatment. Logistic regressions were used to test the association between these beliefs and whether the health worker adhered to malaria testing and treatment guidelines. Results: Of the 1070 individuals who visited a formal health facility during their illness, 82% were tested for malaria. ACT rates for malaria-positive and negative individuals were 89 and 49%, respectively. Overall, 65% of individuals/caregivers believed that the illness was "very likely" malaria. Individuals/caregivers had higher odds of saying that the illness was "very likely" malaria when the individual was treated with ACT, and this was the case both among individuals not tested for malaria [adjusted odds ratio (AOR) 3.42, 95% confidence interval (CI) [1.65 7.10], P = 0.001] and among individuals tested for malaria, regardless of their test result. In addition, 72% of ACT-takers said the drug was "very likely" effective in treating malaria. However, malaria-negative individuals who were treated with ACT had lower odds of saying that the drugs were "very likely" effective than ACT-takers who were not tested or who tested positive for malaria (AOR 0.29, 95% CI [0.13 0.63], P = 0.002). Conclusion: Individuals/caregivers were more likely to believe that the illness was malaria when the patient was treated with ACT, regardless of their test result. Moreover, malaria-negative individuals treated with ACT had lower confidence in the drug than other individuals who took ACT. These results suggest that ensuring health worker adherence to malaria case management guidelines will not only improve ACT targeting, but may also increase patient/caregivers' confidence in malaria testing and treatment. [ABSTRACT FROM AUTHOR]

Background: Health facility-based data reported through routine health information systems form the primary data source for programmatic monitoring and evaluation in most developing countries. The adoption of District Health Information Software (DHIS2) has contributed to improved availability of routine health facility-based data in many low-income countries. An assessment of malaria indicators data reported by health facilities in Kenya during the first 5 years of implementation of DHIS2, from January 2011 to December 2015, was conducted. Methods: Data on 19 malaria indicators reported monthly by health facilities were extracted from the online Kenya DHIS2 database. Completeness of reporting was analysed for each of the 19 malaria indicators and expressed as the percentage of data values actually reported over the expected number; all health facilities were expected to report data for each indicator for all 12 months in a year. Results: Malaria indicators data were analysed for 6235 public and 3143 private health facilities. Between 2011 and 2015, completeness of reporting in the public sector increased significantly for confirmed malaria cases across all age categories (26.5-41.9%, p < 0.0001, in children aged <5 years; 30.6-51.4%, p < 0.0001, in persons aged ≥5 years). Completeness of reporting of new antenatal care (ANC) clients increased from 53.7 to 70.5%, p < 0.0001). Completeness of reporting of intermittent preventive treatment in pregnancy (IPTp) decreased from 64.8 to 53.7%, p < 0.0001 for dose 1 and from 64.6 to 53.4%, p < 0.0001 for dose 2. Data on malaria tests performed and test results were not available in DHIS2 from 2011 to 2014. In 2015, sparse data on microscopy (11.5% for children aged <5 years; 11.8% for persons aged ≥5 years) and malaria rapid diagnostic tests (RDTs) (8.1% for all ages) were reported. In the private sector, completeness of reporting increased significantly for confirmed malaria cases across all age categories (16.7-23.1%, p < 0.0001, in children aged <5 years; 19.4-28.6%, p < 0.0001, in persons aged ≥5 years). Completeness of reporting also improved for new ANC clients (16.2-23.6%, p < 0.0001), and for IPTp doses 1 and 2 (16.6-20.2%, p < 0.0001 and 15.5-20.5%, p < 0.0001, respectively). In 2015, less than 3% of data values for malaria tests performed were reported in DHIS2 from the private sector. Conclusions: There have been sustained improvements in the completeness of data reported for most key malaria indicators since the adoption of DHIS2 in Kenya in 2011. However, major data gaps were identified for the malaria-test indicator and overall low reporting across all indicators from private health facilities. A package of proven DHIS2 implementation interventions and performance-based incentives should be considered to improve private-sector data reporting. [ABSTRACT FROM AUTHOR]

Background: One objective of the Kenya National Malaria Strategy 2009-2017 is scaling access to prompt diagnosis and effective treatment. In 2013, a quality assurance (QA) pilot was implemented to improve accuracy of malaria diagnostics at selected health facilities in low-transmission counties of Kenya. Trends in malaria diagnostic and QA indicator performance during the pilot are described. Methods: From June to December 2013, 28 QA officers provided on-the-job training and mentoring for malaria microscopy, malaria rapid diagnostic tests and laboratory QA/quality control (QC) practices over four 1-day visits at 83 health facilities. QA officers observed and recorded laboratory conditions and practices and cross-checked blood slides for malaria parasite presence, and a portion of cross-checked slides were confirmed by reference laboratories. Results: Eighty (96%) facilities completed the pilot. Among 315 personnel at pilot initiation, 13% (n = 40) reported malaria diagnostics training within the previous 12 months. Slide positivity ranged from 3 to 7%. Compared to the reference laboratory, microscopy sensitivity ranged from 53 to 96% and positive predictive value from 39 to 53% for facility staff and from 60 to 96% and 52 to 80%, respectively, for QA officers. Compared to reference, specificity ranged from 88 to 98% and negative predictive value from 98 to 99% for health-facility personnel and from 93 to 99% and 99%, respectively, for QA officers. The kappa value ranged from 0.48-0.66 for facility staff and 0.57-0.84 for QA officers compared to reference. The only significant test performance improvement observed for facility staff was for specificity from 88% (95% CI 85-90%) to 98% (95% CI 97-99%). QA/QC practices, including use of positive-control slides, internal and external slide cross-checking and recording of QA/QC activities, all increased significantly across the pilot (p < 0.001). Reference material availability also increased significantly; availability of six microscopy job aids and seven microscopy standard operating procedures increased by a mean of 32 percentage points (p < 0.001) and 38 percentage points (p < 0.001), respectively. Conclusions: Significant gains were observed in malaria QA/QC practices over the pilot. However, these advances did not translate into improved accuracy of malaria diagnostic performance perhaps because of the limited duration of the QA pilot implementation. [ABSTRACT FROM AUTHOR]

Background: Important gaps still exist in malaria case management despite implementation of the World Health Organization parasitological diagnosis before treatment recommendation. This calls for evidence-based strategies to improve health providers' adherence to these guidelines. Objective: The goal of this project was to improve adherence of confirmed parasitological diagnosis prior to antimalarial prescription in the outpatient department. Methods: The Joanna Briggs Institute Practical Application of Clinical Evidence System program was used to facilitate collection of baseline and post-audit data. The Getting Research into Practice program was also utilized to analyze the potential barriers and for designing the intervention strategies. This study was done during a 7-month period in an outpatient department of public health facility in Kenya. Results: Baseline and post-implementation audit results comparison indicate that there was a clinically significant improvement in all three criteria. One hundred percent of health providers underwent training on malaria case management, an improvement from 24% at baseline. Almost all (98%) suspected cases for malaria were tested for malaria parasite, and 98% doses of antimalarial drug dispensed had documentation indicating that the malaria test result was positive, an increase of 74%. Conclusion: This study successfully increased the adherence to malaria parasitological confirmation before the treatment recommendation. The interdepartmental collaboration facilitated improvements that led to a reduction in presumptive prescription of antimalarial drugs, antimalarial medication costs, and potentially the emergence of drug resistance. [ABSTRACT FROM AUTHOR]

Objectives: Maximising the impact of community-based programmes requires understanding how supply of, and demand for, the intervention interact at the point of delivery., Design: Post-hoc analysis from a large-scale community health worker (CHW) study designed to increase the uptake of malaria diagnostic testing., Setting: Respondents were identified during a household survey in western Kenya between July 2016 and April 2017., Participants: Household members with fever in the last 4 weeks were interviewed at 12 and 18 months post-implementation. We collected monthly testing data from 244 participating CHWs and conducted semistructured interviews with a random sample of 70 CHWs., Primary and Secondary Outcome Measures: The primary outcome measure was diagnostic testing before treatment for a recent fever. The secondary outcomes were receiving a test from a CHW and tests done per month by each CHW., Results: 55% (n=948 of 1738) reported having a malaria diagnostic test for their recent illness, of which 38.4% were tested by a CHW. Being aware of a local CHW (adjusted OR=1.50, 95% CI: 1.10 to 2.04) and belonging to the wealthiest households (vs least wealthy) were associated with higher testing (adjusted OR=1.53, 95% CI: 1.14 to 2.06). Wealthier households were less likely to receive their test from a CHW compared with poorer households (adjusted OR=0.32, 95% CI: 0.17 to 0.62). Confidence in artemether-lumefantrine to cure malaria (adjusted OR=2.75, 95% CI: 1.54 to 4.92) and perceived accuracy of a malaria rapid diagnostic test (adjusted OR=2.43, 95% CI: 1.12 to 5.27) were positively associated with testing by a CHW. Specific CHW attributes were associated with performing a higher monthly number of tests including formal employment, serving more than 50 households (vs <50) and serving areas with a higher test positivity. On demand side, confidence of the respondent in a test performed by a CHW was strongly associated with seeking a test from a CHW., Conclusion: Scale-up of community-based malaria testing is feasible and effective in increasing uptake among the poorest households. To maximise impact, it is important to recognise factors that may restrict delivery and demand for such services., Trial Registration Number: NCT02461628; Post-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Understanding the availability of rapid diagnostic tests (RDTs) is essential for attaining universal health care and reducing health inequalities. Although routine data helps measure RDT coverage and health access gaps, many healthcare facilities fail to report their monthly diagnostic test data to routine health systems, impacting routine data quality. This study sought to understand whether non-reporting by facilities is due to a lack of diagnostic and/or service provision capacity by triangulating routine and health service assessment survey data in Kenya., Methods: Routine facility-level data on RDT administration were sourced from the Kenya health information system for the years 2018-2020. Data on diagnostic capacity (RDT availability) and service provision (screening, diagnosis, and treatment) were obtained from a national health facility assessment conducted in 2018. The two sources were linked and compared obtaining information on 10 RDTs from both sources. The study then assessed reporting in the routine system among facilities with (i) diagnostic capacity only, (ii) both confirmed diagnostic capacity and service provision and (iii) without diagnostic capacity. Analyses were conducted nationally, disaggregated by RDT, facility level and ownership., Results: Twenty-one per cent (2821) of all facilities expected to report routine diagnostic data in Kenya were included in the triangulation. Most (86%) were primary-level facilities under public ownership (70%). Overall, survey response rates on diagnostic capacity were high (> 70%). Malaria and HIV had the highest response rate (> 96%) and the broadest coverage in diagnostic capacity across facilities (> 76%). Reporting among facilities with diagnostic capacity varied by test, with HIV and malaria having the lowest reporting rates, 58% and 52%, respectively, while the rest ranged between 69% and 85%. Among facilities with both service provision and diagnostic capacity, reporting ranged between 52% and 83% across tests. Public and secondary facilities had the highest reporting rates across all tests. A small proportion of health facilities without diagnostic capacity submitted testing reports in 2018, most of which were primary facilities., Conclusion: Non-reporting in routine health systems is not always due to a lack of capacity. Further analyses are required to inform other drivers of non-reporting to ensure reliable routine health data., (© 2023. The Author(s).)

Background: In western Kenya, not all malaria cases are reported as stipulated in the community case management of malaria (CCMm) strategy. This underreporting affects the equity distribution of malaria commodities and the evaluation of interventions. The current study aimed to evaluate the effectiveness of community health volunteers' active case detection and management of malaria in western Kenya., Methods: Cross-sectional active case detection (ACD) of malaria survey was carried out between May and August 2021 in three eco-epidemiologically distinct zones in Kisumu, western Kenya: Kano Plains, Lowland lakeshore and Highland Plateau. The CHVs conducted biweekly ACD of malaria household visits to interview and examine residents for febrile illness. The Community Health Volunteers (CHVs) performance during the ACD of malaria was observed and interviews done using structured questionnaires., Results: Of the total 28,800 surveyed, 2597 (9%) had fever and associated malaria symptoms. Eco-epidemiological zones, gender, age group, axillary body temperature, bed net use, travel history, and survey month all had a significant association with malaria febrile illness (p < 0.05). The qualification of the CHV had a significant influence on the quality of their service. The number of health trainings received by the CHVs was significantly related to the correctness of using job aid (χ 2  = 6.261, df = 1, p = 0.012) and safety procedures during the ACD activity (χ 2  = 4.114, df = 1, p = 0.043). Male CHVs were more likely than female CHVs to correctly refer RDT-negative febrile residents to a health facility for further treatment (OR = 3.94, 95% CI = 1.85-5.44, p < 0.0001). Most of RDT-negative febrile residents who were correctly referred to the health facility came from the clusters with a CHV having 10 years of experience or more (OR = 1.29, 95% CI = 1.05-1.57, p = 0.016). Febrile residents in clusters managed by CHVs with more than 10 years of experience (OR = 1.82, 95% CI = 1.43-2.31, p < 0.0001), who had a secondary education (OR = 1.53, 95% CI = 1.27-1.85, p < 0.0001), and were over the age of 50 (OR = 1.44, 95% CI = 1.18-1.76, p < 0.0001), were more likely to seek malaria treatment in public hospitals. All RDT positive febrile residents were given anti-malarial by the CHVs, and RDT negatives were referred to the nearest health facility for further treatment., Conclusions: The CHV's years of experience, education level, and age had a significant influence on their service quality. Understanding the qualifications of CHVs can assist healthcare systems and policymakers in designing effective interventions that assist CHVs in providing high-quality services to their communities., (© 2023. The Author(s).)

Background: Odour baits can attract host-seeking Anopheles mosquitoes indoors and outdoors. We assessed the effects of mass deployment of odour-baited traps on malaria transmission and disease burden.Methods: We installed solar-powered odour-baited mosquito trapping systems (SMoTS) to households on Rusinga Island, Lake Victoria, western Kenya (mean population 24 879), in a stepped-wedge cluster-randomised trial. All residents in the completed health and demographic surveillance system were eligible to participate. We used the travelling salesman algorithm to assign all households to a cluster (50 or 51 geographically contiguous households); nine contiguous clusters formed a metacluster. Initially, no cluster had SMoTS (non-intervened). During the course of the intervention roll-out SMoTS were gradually installed cluster by cluster until all clusters had SMoTS installed (intervened). We generated 27 cluster randomisations, with the cluster as unit of randomisation, to establish the order to install the traps in the clusters until all had a SMoTS installed. Field workers and participants were not masked to group allocation. The primary outcome of clinical malaria was monitored through repeated household visits covering the entire population, once before roll-out (baseline) and five times throughout the 2-year roll-out. We measured clinical malaria as fever plus a positive result with a rapid diagnostic test. The SolarMal project was registered on the Dutch Trial Register (NTR 3496).Findings: We enrolled 34 041 participants between April 25, 2012, and March 23, 2015, to 81 clusters and nine metaclusters. 4358 households were provided with SMoTS during roll-out between June 3, 2013, and May 16, 2015. 23 clinical malaria episodes were recorded in intervened clusters and 33 episodes in non-intervened clusters (adjusted effectiveness 40·8% [95% CI -172·8 to 87·1], p=0·5) during the roll-out. Malaria prevalence measured by rapid diagnostic test was 29·8% (95% CI 20·9-38·0) lower in SMoTS clusters (prevalence 23·7%; 1552 of 6550 people) than in non-intervened clusters (prevalence 34·5%; 2002 of 5795 people).Interpretation: The unexpectedly low clinical incidence of malaria during roll-out led to an imprecise estimate of effectiveness from the clinical incidence data. The substantial effect on malaria prevalence is explained by reduction in densities of Anopheles funestus. Odour-baited traps might be an effective malaria intervention.Funding: COmON Foundation. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be a major burden in the endemic regions of Kenya. Health outcomes associated with case management are dependent on the use of appropriate diagnostic methods. Rapid diagnostic tests (RDTs) have provided an important tool to help implement the WHO recommended parasite-based diagnosis in regions where expert microscopy is not available. One of the questions that must be answered when implementing RDTs is whether these tests are useful in a specific endemic region, as well as the most appropriate RDT to use. Data on the sensitivity and specificity of RDT test kits is important information to help guide test selection by national malaria control programmes. Methods: This study evaluated the diagnostic performance of RDTs including First Response (FR), CareStart (CS), SD Bioline (SD), and Binax Now (BN). The performance of these malaria kits was compared to microscopy, the gold standard, for the detection of malaria parasites. The malaria RDTs were also compared to PCR which is a more sensitive reference test. Five-hundred participants were included in the study through community screening (50 %) and testing suspected malaria cases referred from health facilities. Results: Of the 500 participants recruited, 33 % were malaria positive by microscopy while 51.2 % were positive by PCR. Compared to microscopy, the sensitivity of eight RDTs to detect malaria parasites was 90.3-94.8 %, the specificity was 73.3-79.3 %, the positive predictive value was 62.2-68.8 %, and the negative predictive value was 94.3-96.8 %. Compared to PCR, the sensitivity of the RDTs to detect malaria parasites was 71.1-75.4 %, the specificity was 80.3-84.4 %, the positive predictive value was 80.3-83.3 %, and the negative predictive value was 73.7-76.1 %. The RDTs had a moderate measure of agreement with both microscopy (>80.1 %) and PCR (>77.6 %) with a κ > 0.6. Conclusion: The performance of the evaluated RDTs using field samples was moderate; hence they can significantly improve the quality of malaria case management in endemic regions in Kenya by ensuring appropriate treatment of malaria positive individuals and avoiding indiscriminate use of anti-malarial drugs for parasite negative patients. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.Methods and Findings: Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June-6 July 2012) and 16 wk (21 August-10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI -1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265). We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75). Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms. In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms. Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons.Conclusions: Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear.Trial Registration: ClinicalTrials.gov NCT01575613. [ABSTRACT FROM AUTHOR]

Background: Every year, more than 32 million pregnancies in sub-Saharan Africa are at risk of malaria infection and its adverse consequences. The effectiveness of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy recommended by WHO is threatened by high levels of parasite resistance. We aimed to assess the efficacy and safety of two alternative strategies: intermittent screening with malaria rapid diagnostic tests and treatment of women who test positive with dihydroartemisinin-piperaquine, and intermittent preventive treatment with dihydroartemisinin-piperaquine.Methods: We did this open-label, three-group, randomised controlled superiority trial at four sites in western Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-negative pregnant women between 16 and 32 weeks' gestation were randomly assigned (1:1:1), via computer-generated permuted-block randomisation (block sizes of three, six, and nine), to receive intermittent screening and treatment with dihydroartemisinin-piperaquine, intermittent preventive treatment with dihydroartemisinin-piperaquine, or intermittent preventive treatment with sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study coordinator were aware of treatment allocation, but allocation was concealed from study investigators, delivery unit nurses, and laboratory staff. The primary outcome was malaria infection at delivery, defined as a composite of peripheral or placental parasitaemia detected by placental histology, microscopy, or rapid diagnostic test. The primary analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01669941.Findings: Between Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to receive intermittent screening and treatment with dihydroartemisinin-piperaquine (n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine (n=516), or intermittent preventive treatment with sulfadoxine-pyrimethamine (n=515); 1368 (88%) women comprised the intention-to-treat population for the primary endpoint. Prevalence of malaria infection at delivery was lower in the intermittent preventive treatment with dihydroartemisinin-piperaquine group than in the intermittent preventive treatment with sulfadoxine-pyrimethamine group (15 [3%] of 457 women vs 47 [10%] of 459 women; relative risk 0·32, 95% CI 0·18-0·56; p<0·0001), but not in the intermittent screening and treatment with dihydroartemisinin-piperaquine group (57 [13%] of 452 women; 1·23, 0·86-1·77; p=0·26). Compared with intermittent preventive treatment with sulfadoxine-pyrimethamine, intermittent preventive treatment with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria infection during pregnancy (192·0 vs 54·4 events per 100 person-years; incidence rate ratio [IRR] 0·28, 95% CI 0·22-0·36; p<0·0001) and clinical malaria during pregnancy (37·9 vs 6·1 events; 0·16, 0·08-0·33; p<0·0001), whereas intermittent screening and treatment with dihydroartemisinin-piperaquine was associated with a higher incidence of malaria infection (232·0 events; 1·21, 1·03-1·41; p=0·0177) and clinical malaria (53·4 events; 1·41, 1·00-1·98; p=0·0475). We recorded 303 maternal and infant serious adverse events, which were least frequent in the intermittent preventive treatment with dihydroartemisinin-piperaquine group.Interpretation: At current levels of rapid diagnostic test sensitivity, intermittent screening and treatment is not a suitable alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine in the context of high sulfadoxine-pyrimethamine resistance and malaria transmission. However, dihydroartemisinin-piperaquine is a promising alternative drug to replace sulfadoxine-pyrimethamine for intermittent preventive treatment. Future studies should investigate the efficacy, safety, operational feasibility, and cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine.Funding: The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine. [ABSTRACT FROM AUTHOR]

Background: Inappropriate treatment of non-malaria fevers with artemisinin-based combination therapies (ACTs) is a growing concern, particularly in light of emerging artemisinin resistance, but it is a behavior that has proven difficult to change. Pay for performance (P4P) programs have generated interest as a mechanism to improve health service delivery and accountability in resource-constrained health systems. However, there has been little experimental evidence to establish the effectiveness of P4P in developing countries. We tested a P4P strategy that emphasized parasitological diagnosis and appropriate treatment of suspected malaria, in particular reduction of unnecessary consumption of ACTs.Methods: A random sample of 18 health centers was selected and received a refresher workshop on malaria case management. Pre-intervention baseline data was collected from August to September 2012. Facilities were subsequently randomized to either the comparison (n = 9) or intervention arm (n = 9). Between October 2012 and November 2013, facilities in the intervention arm received quarterly incentive payments based on seven performance indicators. Incentives were for use by facilities rather than as payments to individual providers. All non-pregnant patients older than 1 year of age who presented to a participating facility and received either a malaria test or artemether-lumefantrine (AL) were eligible to be included in the analysis. Our primary outcome was prescription of AL to patients with a negative malaria diagnostic test (n = 11,953). Our secondary outcomes were prescription of AL to patients with laboratory-confirmed malaria (n = 2,993) and prescription of AL to patients without a malaria diagnostic test (analyzed at the cluster level, n = 178 facility-months).Results: In the final quarter of the intervention period, the proportion of malaria-negative patients in the intervention arm who received AL was lower than in the comparison arm (7.3% versus 10.9%). The improvement from baseline to quarter 4 in the intervention arm was nearly three times that of the comparison arm (ratio of adjusted odds ratios for baseline to quarter 4 = 0.36, 95% CI: 0.24-0.57). The rate of prescription of AL to patients without a test was five times lower in the intervention arm (adjusted incidence rate ratio = 0.18, 95% CI: 0.07-0.48). Prescription of AL to patients with confirmed infection was not significantly different between the groups over the study period.Conclusions: Facility-based incentives coupled with training may be more effective than training alone and could complement other quality improvement approaches.Trial Registration: This study was registered with ClinicalTrials.gov (NCT01809873) on 11 March 2013. [ABSTRACT FROM AUTHOR]

Introduction. Overdiagnosis of malaria cases hampers malaria control in developing countries. Due to lack of diagnostics, febrile cases are treated using signs and symptoms. We evaluated an intervention to minimize overdiagnosis in Ijara sub-County, Kenya. Methods. Health workers were trained on case management and rapid diagnostic tests provided in late 2011. Malaria outpatient morbidity was assessed a year before and after the intervention coupled with data on rapid diagnostic tests consumption. Results. The number of diagnosed malaria cases decreased from 15,615 in 2011 to 1,892 in 2012. This represents an 87.8% decrease. There was a significant difference in number of diagnosed monthly malaria cases during the pre-intervention (Mean = 1,299, SD = 550.4) and post-intervention periods (Mean = 158, SD = 160.9, t (12.9) = 6.9, p = .000, two tailed). Mean monthly consumption of rapid diagnostic tests was 730, with 5.2% testing positive. Conclusion. This intervention reduced overdiagnosis and overtreatment of malaria cases. [ABSTRACT FROM AUTHOR]

Background: The prevalence of malaria parasites in adults in Africa is less well researched than in children. Therefore, a demographic surveillance site was used to conduct a household survey of adults in the malaria endemic area of Maseno division in Kisumu County near Lake Victoria. Methods: A random survey of 1,190 adults living in a demographic health surveillance site in a malaria endemic area of 70,805 population size was conducted, measuring presence of malaria parasites by slide microscopy. Data were analysed using STATA to calculate the prevalence of malaria and associated risk factors. Results: The adult prevalence of presence of malaria parasites in Maseno was 28% (95% CI: 25.4-31.0%). Gender was a significant sociodemographic risk factor in both univariate (OR 1.5, p = 0.005) and multivariate (OR 1.4, p = 0.019) analyses. Females were 50% more likely to have malaria than men. Conclusions: Presence of malaria parasites is common in the adult population of this endemic area, and the rate is greatly increased in women. The presence of such an adult pool of malaria parasites represents a key reservoir factor in transmission of parasites to children, and is relevant for plans to eradicate malaria. [ABSTRACT FROM AUTHOR]

Asymptomatic malaria infections represent a major challenge in malaria control and elimination in Africa. They are reservoirs of malaria parasite that can contribute to disease transmission. Therefore, identification and control of asymptomatic infections are important to make malaria elimination feasible. In this study, we investigated the extent and distribution of asymptomatic malaria in Western Kenya and examined how varying parasitemia affects performance of diagnostic methods including microscopy, conventional PCR, and quantitative PCR. In addition, we compared parasite prevalence rates and parasitemia levels with respect to topography and age in order to explore factors that influence malaria infection. Over 11,000 asymptomatic blood samples from children and adolescents up to 18 years old representing broad areas of Western Kenya were included. Quantitative PCR revealed the highest parasite positive rate among all methods and malaria prevalence in western Kenya varied widely from less than 1% to over 50%. A significantly lower parasitemia was detected in highland than in lowland samples and this contrast was also observed primarily among submicroscopic samples. Although we found no correlation between parasitemia level and age, individuals of younger age group (aged <14) showed significantly higher parasite prevalence. In the lowlands, individuals of aged 5–14 showed significantly higher prevalence than those under age 5. Our findings highlight the need for a more sensitive and time-efficient assay for asymptomatic malaria detection particularly in areas of low-transmission. Combining QPCR with microscopy can enhance the capacity of detecting submicroscopic asymptomatic malaria infections. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that supply chain costs are a significant proportion of total programme costs. Nevertheless, the costs of delivering specific products are poorly understood and ballpark estimates are often used to inadequately plan for the budgetary implications of supply chain expenses. The purpose of this research was to estimate the country level costs of the public sector supply chain for artemisinin-based combination therapy (ACT) and rapid diagnostic tests (RDTs) from the central to the peripheral levels in Benin and Kenya. Methods: A micro-costing approach was used and primary data on the various cost components of the supply chain was collected at the central, intermediate, and facility levels between September and November 2013. Information sources included central warehouse databases, health facility records, transport schedules, and expenditure reports. Data from document reviews and semi-structured interviews were used to identify cost inputs and estimate actual costs. Sampling was purposive to isolate key variables of interest. Survey guides were developed and administered electronically. Data were extracted into Microsoft Excel®, and the supply chain cost per unit of ACT and RDT distributed by function and level of system was calculated. Results: In Benin, supply chain costs added USD 0.2011 to the initial acquisition cost of ACT and USD 0.3375 to RDTs (normalized to USD 1). In Kenya, they added USD 0.2443 to the acquisition cost of ACT and USD 0.1895 to RDTs (normalized to USD 1). Total supply chain costs accounted for more than 30% of the initial acquisition cost of the products in some cases and these costs were highly sensitive to product volumes. The major cost drivers were found to be labour, transport, and utilities with health facilities carrying the majority of the cost per unit of product. Conclusions: Accurate cost estimates are needed to ensure adequate resources are available for supply chain activities. Product volumes should be considered when costing supply chain functions rather than dollar value. Further work is needed to develop extrapolative costing models that can be applied at country level without extensive micro-costing exercises. This will allow other countries to generate more accurate estimates in the future. [ABSTRACT FROM AUTHOR]

Background: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT). Methods and Findings: 450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns’ cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib. Conclusions: There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women. [ABSTRACT FROM AUTHOR]

Background Microscopy and rapid diagnostic tests (RDTs) are common tools for diagnosing malaria, but are deficient in detecting low Plasmodium parasitaemia. A novel molecular diagnostic tool (nPCR-HRM) that combines the sensitivity and specificity of nested PCR (nPCR) and direct PCR-high resolution melting analysis (dPCR-HRM) was developed. To evaluate patterns of anti-malarial drug administration when no parasites are detected, nPCR-HRM was employed to screen blood samples for low parasitaemia from febrile patients without microscopically detectable Plasmodium infections in a rural malaria-endemic setting. Methods Blood samples (n = 197) were collected in two islands of Lake Victoria, Kenya, from febrile patients without Plasmodium detectable by microscopy or RDTs. 18S rRNA gene sequences were amplified from extracted DNA by nPCR-HRM, nPCR, and dPCR-HRM to detect and differentiate Plasmodium parasites. The limits of detection (LoD) were compared using serial dilutions of the WHO International Standard for P. falciparum DNA. Data on administration of anti-malarials were collected to estimate prescription of anti-malarial drugs to patients with and without low parasitaemia Plasmodium infections. Results The coupled nPCR-HRM assay detected Plasmodium parasites with greater sensitivity (LoD =236 parasites/mL) than either nPCR (LoD =4,700 parasites/mL) or dPCR-HRM (LoD =1,490 parasites/mL). Moreover, nPCR-HRM detected and differentiated lowparasitaemia infections in significantly greater proportions of patients than did either nPCR or dPCR-HRM (p-value <0.001). Among these low-parasitaemia infections, 67.7% of patients were treated with anti-malarials, whereas 81.5% of patients not infected with Plasmodium parasites were treated with anti-malarials. Conclusions The enhanced sensitivity of nPCR-HRM demonstrates limitations of differential febrile illness diagnostics in rural malaria endemic settings that confound epidemiological estimates of malaria, and lead to inadvertent misadministration of anti-malarial drugs. This is the first study that employs low-parasitaemia Plasmodium diagnostics to quantify the prescription of anti-malarial drugs to both non-malaria febrile patients and patients with low-parasitaemia Plasmodium infections. nPCR-HRM enhances low-parasitaemia malaria diagnosis and can potentially surmount the deficiencies of microscopy and RDT-based results in determining low-parasitaemia Plasmodium infection rates for evaluating malaria elimination efforts. The findings highlight the need for improved differential diagnostics of febrile illness in remote malaria endemic regions. [ABSTRACT FROM AUTHOR]

Objectives: To examine how drug shop clients' expenditures are affected by subsidies for malaria diagnostic testing and for malaria treatment, and also to examine how expenditures vary by clients' malaria test result and by the number of medications they purchased., Design: Secondary cross-sectional analysis of survey responses from a randomised controlled trial., Setting: The study was conducted in twelve private drug shops in Western Kenya., Participants: We surveyed 836 clients who visited the drug shops between March 2018 and October 2019 for a malaria-like illness. This included children >1 year of age if they were physically present and accompanied by a parent or legal guardian., Interventions: Subsidies for malaria diagnostic testing and for malaria treatment (conditional on a positive malaria test result)., Primary and Secondary Outcome Measures: Expenditures at the drug shop in Kenya shillings (Ksh)., Results: Clients who were randomised to a 50% subsidy for malaria rapid diagnostic tests (RDTs) spent approximately Ksh23 less than those who were randomised to no RDT subsidy (95% CI (-34.6 to -10.7), p=0.002), which corresponds approximately to the value of the subsidy (Ksh20). However, clients randomised to receive free treatment (artemisinin combination therapies (ACTs)) if they tested positive for malaria had similar spending levels as those randomised to a 67% ACT subsidy conditional on a positive test. Expenditures were also similar by test result, however, those who tested positive for malaria bought more medications than those who tested negative for malaria while spending approximately Ksh15 less per medication (95% CI (-34.7 to 3.6), p=0.102)., Conclusions: Our results suggest that subsidies for diagnostic health products may result in larger household savings than subsidies on curative health products. A better understanding of how people adjust their behaviours and expenditures in response to subsidies could improve the design and implementation of subsidies for health products., Trial Registration Number: NCT03810014., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background The commonly accepted gold standard diagnostic method for detecting malaria is a microscopic reading of Giemsa-stained blood films. However, symptomatic diagnosis remains the basis of therapeutic care for the majority of febrile patients in malaria endemic areas. This study aims to compare the discrepancy in malaria and anaemia burdens between symptomatic diagnosed patients with those diagnosed through the laboratory. Methods Data were collected from Western Kenya during a follow-up study of 887 children with suspected cases of malaria visiting the health facilities. In the laboratory, blood samples were analysed for malaria parasite and haemoglobin levels. Differences in malaria prevalence between symptomatic diagnosis and laboratory diagnosis were analysed by Chi-square test. Bayesian probabilities were used for the approximation of the malaria and anaemia burdens. Regression analysis was applied to: (1) determine the relationships between haemoglobin levels, and malaria parasite density and (2) relate the prevalence of anaemia and the prevalence of malaria. Results The prevalence of malaria and anaemia ranged from 10% to 34%, being highest during the rainy seasons. The predominant malaria parasite was P. falciparum (92.3%), which occurred in higher density in children aged 2-5 years. Fever, high temperature, sweating, shivering, vomiting and severe headache symptoms were associated with malaria during presumptive diagnosis. After conducting laboratory diagnosis, lower malaria prevalence was reported among the presumptively diagnosed patients. Surprisingly, there were no attempts to detect anaemia in the same cohort. There was a significant negative correlation between Hb levels and parasite density. We also found a positive correlation between the prevalence of anaemia and the prevalence of malaria after laboratory diagnosis indicating possible co-occurrence of malaria and anaemia. Conclusion Symptomatic diagnosis of malaria overestimates malaria prevalence, but underestimates the anaemia burden in children. Good clinical practice dictates that a laboratory should confirm the presence of parasites for all suspected cases of malaria. [ABSTRACT FROM AUTHOR]

: Katherine Halliday and colleagues conducted a cluster randomized controlled trial in Kenyan school children in an area of low to moderate malaria transmission to investigate the effect of intermittent screening and treatment of malaria on health and education. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: Detection of malaria parasitaemia in samples that are negative by rapid diagnostic tests (RDTs) requires resource-intensive molecular tools. While pooled testing using a two-step strategy provides a cost-saving alternative to the gold standard of individual sample testing, statistical adjustments are needed to improve accuracy of prevalence estimates for a single step pooled testing strategy., Methods: A random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in Asembo, Gem, and Karemo, western Kenya. Samples were tested for malaria individually and in pools of five, 934 pools, by one-step quantitative polymerase chain reaction (qPCR). Maximum likelihood approaches were used to estimate subpatent parasitaemia (RDT-negative, qPCR-positive) prevalence by pooling, assuming poolwise sensitivity and specificity was either 100% (strategy A) or imperfect (strategy B). To improve and illustrate the practicality of this estimation approach, a validation study was constructed from pools allocated at random into main (734 pools) and validation (200 pools) subsets. Prevalence was estimated using strategies A and B and an inverse-variance weighted estimator and estimates were weighted to account for differential sampling rates by area., Results: The prevalence of subpatent parasitaemia was 14.5% (95% CI 13.6-15.3%) by individual qPCR, 9.5% (95% CI (8.5-10.5%) by strategy A, and 13.9% (95% CI 12.6-15.2%) by strategy B. In the validation study, the prevalence by individual qPCR was 13.5% (95% CI 12.4-14.7%) in the main subset, 8.9% (95% CI 7.9-9.9%) by strategy A, 11.4% (95% CI 9.9-12.9%) by strategy B, and 12.8% (95% CI 11.2-14.3%) using inverse-variance weighted estimator from poolwise validation. Pooling, including a 20% validation subset, reduced costs by 52% compared to individual testing., Conclusions: Compared to individual testing, a one-step pooled testing strategy with an internal validation subset can provide accurate prevalence estimates of PCR-positivity among RDT-negatives at a lower cost., (© 2022. The Author(s).)

Background: Malaria remains a public health problem in Kenya despite sustained interventions deployed by the government. One of the major impediments to effective malaria control is a lack of accurate diagnosis and effective treatment. This study was conducted to assess clinical malaria incidence and treatment seeking profiles of febrile cases in western Kenya., Methods: Active case detection of malaria was carried out in three eco-epidemiologically distinct zones topologically characterized as lakeshore, hillside, and highland plateau in Kisumu County, western Kenya, from March 2020 to March 2021. Community Health Volunteers (CHVs) conducted biweekly visits to residents in their households to interview and examine for febrile illness. A febrile case was defined as an individual having fever (axillary temperature ≥ 37.5 °C) during examination or complaints of fever and other nonspecific malaria related symptoms 1-2 days before examination. Prior to the biweekly malaria testing by the CHVs, the participants' treatment seeking methods were based on their behaviors in response to febrile illness. In suspected malaria cases, finger-prick blood samples were taken and tested for malaria parasites with ultra-sensitive Alere ® malaria rapid diagnostic tests (RDT) and subjected to real-time polymerase chain reaction (RT-PCR) for quality control examination., Results: Of the total 5838 residents interviewed, 2205 residents had high temperature or reported febrile illness in the previous two days before the visit. Clinical malaria incidence (cases/1000people/month) was highest in the lakeshore zone (24.3), followed by the hillside (18.7) and the highland plateau zone (10.3). Clinical malaria incidence showed significant difference across gender (χ 2  = 7.57; df = 2, p = 0.0227) and age group (χ 2  = 58.34; df = 4, p < 0.0001). Treatment seeking patterns of malaria febrile cases showed significant difference with doing nothing (48.7%) and purchasing antimalarials from drug shops (38.1%) being the most common health-seeking pattern among the 2205 febrile residents (χ 2  = 21.875; df = 4, p < 0.0001). Caregivers of 802 school-aged children aged 5-14 years with fever primarily sought treatment from drug shops (28.9%) and public hospitals (14.0%), with significant lower proportions of children receiving treatment from traditional medication (2.9%) and private hospital (4.4%) (p < 0.0001). There was no significant difference in care givers' treatment seeking patterns for feverish children under the age of five (p = 0.086). Residents with clinical malaria cases in the lakeshore and hillside zones sought treatment primarily from public hospitals (61.9%, 60/97) traditional medication (51.1%, 23/45) respectively (p < 0.0001). However, there was no significant difference in the treatment seeking patterns of highland plateau residents with clinical malaria (p = 0.431).The main factors associated with the decision to seek treatment were the travel distance to the health facility, the severity of the disease, confidence in the treatment, and affordability., Conclusion: Clinical malaria incidence remains highest in the Lakeshore (24.3cases/1000 people/month) despite high LLINs coverage (90%). The travel distance to the health facility, severity of disease and affordability were mainly associated with 80% of residents either self-medicating or doing nothing to alleviate their illness. The findings of this study suggest that the Ministry of Health should strengthen community case management of malaria by providing supportive supervision of community health volunteers to advocate for community awareness, early diagnosis, and treatment of malaria., (© 2022. The Author(s).)

Background: Rapid Diagnostic Tests (RDTs) have become the cornerstone for the management of malaria in many endemic settings, but their use is constrained for several reasons: (i) persistent malaria antigen (histidine-rich protein 2; HRP2) leading to false positive test results; (ii) hrp2 deletions leading to false negative PfHRP2 results; and (iii) limited sensitivity with a detection threshold of around 100 parasites/μl blood (pLDH- and HRP2-based) leading to false negative tests. Microscopy is still the gold standard for malaria diagnosis, and allows for species determination and quantitation, but requires trained microscopists, maintained microscopes and has detection limit issues. Consequently, there is a pressing need to develop and evaluate more sensitive and accurate diagnostic tests. To address this need we have developed a direct on blood mini PCR-NALFIA test that combines the benefits of molecular biology with low infrastructural requirements and extensive training., Methods: This is a Phase 3 diagnostic evaluation in 5 African countries. Study sites (Sudan, Ethiopia, Burkina, Kenya and Namibia) were selected to ensure wide geographical coverage of Africa and to address various malaria epidemiological contexts ranging from high transmission to near elimination settings with different clinical scenarios and diagnostic challenges. Study participants will be enrolled at the study health facilities after obtaining written informed consent. Diagnostic accuracy will be assessed following the WHO/TDR guidelines for the evaluation of diagnostics and reported according to STARD principles. Due to the lack of a 100% specific and sensitive standard diagnostic test for malaria, the sensitivity and specificity of the new test will be compared to the available diagnostic practices in place at the selected sites and to quantitative PCR as the reference test., Discussion: This phase 3 study is designed to validate the clinical performance and feasibility of implementing a new diagnostic tool for the detection of malaria in real clinical settings. If successful, the proposed technology will improve the diagnosis of malaria. Enrolment started in November 2022 (Kenya) with assessment of long term outcome to be completed by 2023 at all recruitment sites., Trial Registration: Pan African Clinical Trial Registry (www.pactr.org) PACTR202202766889963 on 01/02/2022 and ISCRTN (www.isrctn.com/) ISRCTN13334317 on 22/02/2022., Competing Interests: The authors have declared that no competing interests exist.

Background: Simple and accurate diagnosis is a key component of malaria control programmes. Microscopy is the current gold standard, however it requires extensive training and the results largely rely on the skill of the microscopists. Malaria rapid diagnostic tests (RDT) can be performed with minimal training and offer timely diagnosis, but results are not quantitative. Moreover, some Plasmodium falciparum parasites have evolved and can no longer be detected by existing RDT. Developed by the Sysmex Corporation, the XN-31 prototype (XN-31p) is an automated haematology analyser capable of detecting Plasmodium-infected erythrocytes and providing species differentiation and stage specific parasite counts in venous blood samples without any preparation in approximately one minute. However, factors such as stable electricity supply in a temperature-controlled room, cost of the instrument and its initial set-up, and need for proprietary reagents limit the utility of the XN-31p across rural settings. To overcome some of these limitations, a hub and spoke diagnosis model was designed, in which peripheral health facilities were linked to a central hospital where detection of Plasmodium infections by the XN-31p would take place. To explore the feasibility of this concept, the applicability of capillary blood samples with the XN-31p was evaluated with respect to the effect of sample storage time and temperature on the stability of results., Methods: Paired capillary and venous blood samples were collected from 169 malaria-suspected outpatients in Homa Bay County Referral Hospital, Kenya. Malaria infections were diagnosed with the XN-31p, microscopy, RDT, and PCR. Capillary blood samples were remeasured on the XN-31p after 24 h of storage at either room (15-25 °C) or chilled temperatures (2-8 °C)., Results: Identical results in malaria diagnosis were observed between venous and capillary blood samples processed immediately after collection with the XN-31p. Relative to PCR, the sensitivity and specificity of the XN-31p with capillary blood samples were 0.857 and 1.000, respectively. Short-term storage of capillary blood samples at chilled temperatures had no adverse impact on parasitaemia and complete blood counts (CBC) measured by the XN-31p., Conclusion: These results demonstrate the potential of the XN-31p to improve routine malaria diagnosis across remote settings using a hub and spoke model., (© 2022. The Author(s).)

We studied the effect on malaria incidence, mosquito abundance, net efficacy, net use rate, chemical analysis, and holes of a long lasting insecticide treated bed net (Netprotect) in western Kenya, 2007-2010. Nets were hung in 150 households 6 months before they were hung in a second, 2 km away. Indoor resting densities were monitored by pyrethrum spray catch and malaria cases by passive detection using clinical manifestations and rapid diagnostic test. The probability of finding An. arabiensis in the control area was 2.6 times higher than that in intervention area during the first 6 months. Human blood feeding index of Anopheles funestus declined 17%. After bed nets were hung in the second area, malaria incidence declined 25% down to the level in the first area. Incidence remained at this low level for 2 years. 90% of collected nets were efficacious after 3-year use. Deltamethrin dosage declined from 1.9 to 0.5 g/kg over 3 years. Attrition rate after 3 years was 21%. WHO hole index changed from 333 to 114 to 381 over the three years. This index summarizes the numbers of holes in size categories and multiplies with the mean hole area per category. It is very sensitive to the impact of big holes in a few nets. [ABSTRACT FROM AUTHOR]

Background: Health facility stock-outs of life saving malaria medicines are common across Africa. Innovative ways of addressing this problem are urgently required. We evaluated whether SMS based reporting of stocks of artemetherlumefantrine (AL) and rapid diagnostic tests (RDT) can result in reduction of stock-outs at peripheral facilities in Kenya. Methods/Findings: All 87 public health facilities in five Kenyan districts were included in a 26 week project. Weekly facility stock counts of four AL packs and RDTs were sent via structured incentivized SMS communication process from health workers' personal mobile phones to a web-based system accessed by district managers. The mean health facility response rate was 97% with a mean formatting error rate of 3%. Accuracy of stock count reports was 79% while accuracy of stock-out reports was 93%. District managers accessed the system 1,037 times at an average of eight times per week. The system was accessed in 82% of the study weeks. Comparing weeks 1 and 26, stock-out of one or more AL packs declined by 38 percentage-points. Total AL stock-out declined by 5 percentage-points and was eliminated by the end of the project. Stock-out declines of individual AL packs ranged from 14 to 32 percentage-points while decline in RDT stock-outs was 24 percentage-points. District managers responded to 44% of AL and 73% of RDT stock-out signals by redistributing commodities between facilities. In comparison with national trends, stock-out declines in study areas were greater, sharper and more sustained. Conclusions: Use of simple SMS technology ensured high reporting rates of reasonably accurate, real-time facility stock data that were used by district managers to undertake corrective actions to reduce stock-outs. Future work on stock monitoring via SMS should focus on assessing response rates without use of incentives and demonstrating effectiveness of such interventions on a larger scale. [ABSTRACT FROM AUTHOR]

Background. The common symptoms of malaria reduce the specificity of clinical diagnosis. Presumptive treatment is conventional but can lead to overdiagnosis of malaria, delay of appropriate treatment, overprescription of antimalarials, and drug resistance. Routine use of diagnostic tests can address many of these concerns. Though treatment is often procured from retailers, there is low availability of rapid diagnostic tests for malaria (MRDTs), a simple, inexpensive, and accurate diagnostic solution. We know little about the challenges to expanding access to diagnostics through these outlets. Methods. To understand the perceptions of the benefits and challenges to selling rapid diagnostic tests for malaria, we conducted focus group discussions with antimalarial retailers who serve the residents of the Webuye Health and Demographic Surveillance Site in western Kenya. Results. Medicine retailers perceived MRDTs to be beneficial to their customers and businesses but also included cost, fear of the tests, risks of selftreatment, and regulatory concerns among the challenges to using and selling MRDTs. Conclusion. MRDTs represent a viable approach to increase access to malaria diagnostic testing. Medicine retailers are eager for MRDTs to be made available to them. However, certain challenges remain to implementation in retail outlets and should be addressed in advance. [ABSTRACT FROM AUTHOR]

Objective: The objective was to describe the relationship between the location of care, the malaria test result, and the type of medicine consumed for the fever, and to determine whether community-based access to malaria testing reduced polypharmacy . Methods: This is a secondary analysis of a cluster-randomized trial of an intervention designed to increase diagnostic testing and targeting of Artemesinin Combined Therapies (ACTs). Data collected at baseline, 12, and 18 months were analyzed to determine the impact of diagnostic testing on drug consumption patterns among febrile individuals. Results: Of the 5,756 participants analyzed, 60.1% were female, 42% were aged 5-17 years, and 58.1% sought care for fever in a retail outlet. Consumption of both ACT and antibiotics was 22.1% ( n = 443/2008) at baseline. At endline, dual consumption had declined to 16.6%. There was reduced antibiotic consumption among those testing positive for malaria (39.5%-26.5%) and those testing negative (63.4%-55.1%), accompanied by a substantial decline in ACT use among malaria-negative participants. Conclusion: Diagnostic testing for malaria reduces dual consumption of ACTs and antibiotics, especially among those testing outside the formal healthcare sector., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laktabai, Platt, Turner, Saran, Kipkoech, Menya and O’Meara.)

Objectives: To investigate factors associated with hospital length of stay (LOS) in patients admitted with suspected malaria using a competing risk approach., Setting: County government referrals and major faith-based hospitals in Kenya in 2018., Design: Secondary analysis of a cross-sectional survey data., Participants: Data were extracted from 2396 medical records of patients admitted with suspected malaria at 90 hospitals., Outcome Measures: LOS, defined as time to discharge, was the primary event of interest, and time to death was the competing event against patient factors assessed during admission and hospitalisation., Results: Among the patients analysed, 2283 were discharged, 49 died and 64 were censored. The median LOS was 4 days (IQR: 3-6 days). The cumulative incidence of discharge significantly decreased (p<0.05) by 12.7% (subdistribution-HR (SDHR): 0.873; 95% CI 0.789 to 0.967) when the respiratory rate was assessed, by 14.1% (SDHR 0.859; 95% CI 0.754 to 0.978) when oxygen saturation was monitored, by 23.1% (SDHR 0.769; 95% CI 0.709 to 0.833) and 23.4% (SDHR 0.766; 95% CI 0.704 to 0.833) when haemoglobin/haematocrit and glucose/random blood sugar were performed, respectively, and by 30.4% (SDHR 0.696; 95% CI 0.626 to 0.774) when patients had at least one clinical feature of severe malaria. Conversely, patients with confirmed severe malaria and those treated with injectable artesunate had a significantly increased cumulative incidence of discharge by 21.4% (SDHR 1.214; 95% CI 1.082 to 1.362) and 33.9% (SDHR 1.339; 95% CI 1.184 to 1.515), respectively., Conclusions: Factors of inpatient clinical processes that influence hospital LOS were identified. These can be targeted during quality improvement interventions to enhance health service delivery in Kenya. Early recognition and appropriate management of the signs of malaria severity could greatly affect beneficial outcomes. Strengthening clinical practices and nursing care according to national case management guidelines should be a priority for malaria control managers in Kenya., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)